Opioid dependence (OD) is a common, chronic, relapsing addiction with a substantial genetic component. Central to the neurobiology of OD is the mu opioid receptor (MOR), through which most of the rewarding effects of opioids are mediated. The goal of this project is to enhance our understanding of MOR in OD through linkage disequilibrium (LD) genetics studies of OD, using novel candidate genes, MOR interacting proteins (MORIPs). MOR exists as a complex with multiple binding partners (MORIPs) which mediate the signal transduction process, as well as receptor trafficking and desensitization. Relatively few MORIPs are known. Using existing MORIPs as well as novel ones identified through an independent collaboration, we will conduct a case-control association analysis of these known MORIPs and newly-defined MORIPs. We have assembled a set of DNA samples and clinical information from ~ 1500 OD individuals, whose data and biopecimens are in a central NIDA repository. In addition, we have access to ~ 4500 control DNA samples and clinical information from an NIMH repository. Using these resources, MORIP genes will be assessed for roles in genetic susceptibility to OD. Through this project, our understanding of the role of MOR in OD will be enhanced, opening new avenues for treatment of this common and severe addiction.